Improving safe medication use by decreasing preventable adverse drug events (ADEs) is a fundamental priority for transforming the U.S. health care system. The National Action Plan for ADE Prevention (NAP) seeks to support providers, systems and researchers in ensuring the safest care of patients by preventing ADEs from the high priority medication classes of anticoagulants, diabetes agents and opioids. The evidence base for how to effectively prevent or mitigate risk factors for ADEs in the outpatient setting is underdeveloped and there are limited examples of engaging patients in the safety improvement process. The proposed project is a natural evolution of medication safety (MS) research in PPRNet, an AHRQ Center for Primary Care Research and Learning at the Medical University of South Carolina, and consistent with its 15-year history of translating research into real world primary care practice. The project aims to first, clarify risk factors for ADEs from high priority medications through a literature review and translate them into a working set of clinical quality measures that can be implemented in primary care and second, use a community engaged action (CEA) research approach to test the impact of a refined set of preventive strategies for ADEs on practice performance on clinical quality measures in a group-randomized trial. Three significant innovations in the proposed method are: 1) identification of primary care- relevant ADE risk factors for HPM and strategies to prevent them, 2) development of acceptable, reliable and valid ADE CQMs using a modified Delphi method among primary care providers and 3) inclusion of patients in a community engaged action research intervention among real world primary care practices. PPRNet investigators and member practice communities are uniquely qualified to meet the objectives of this program announcement in order to address the prevention of harm and promote standardized and idealized practices and behaviors. Outcomes from this project will address key problems in the existing outpatient safety research paradigm by engaging primary care patients, non-professional caregivers, providers and practice staff in each aim and the multi-method plan for dissemination.